PT  - JOURNAL ARTICLE
AU  - Goodin, D.S.
AU  - Reder, A.T.
AU  - Ebers, G.C.
AU  - Cutter, G.
AU  - Kremenchutzky, M.
AU  - Oger, J.
AU  - Langdon, D.
AU  - Rametta, M.
AU  - Beckmann, K.
AU  - DeSimone, T.M.
AU  - Knappertz, V.
TI  - Survival in MS
AID  - 10.1212/WNL.0b013e3182535cf6
DP  - 2012 Apr 24
TA  - Neurology
PG  - 1315--1322
VI  - 78
IP  - 17
4099  - http://n.neurology.org/content/78/17/1315.short
4100  - http://n.neurology.org/content/78/17/1315.full
SO  - Neurology2012 Apr 24; 78
AB  - Objective: To examine the effects of interferon beta (IFNβ)-1b on all-cause mortality over 21 years in the cohort of 372 patients who participated in the pivotal randomized clinical trial (RCT), retaining (in the analysis) the original randomized treatment-assignments. Methods: For this randomized long-term cohort study, the primary outcome, defined before data collection, was the comparison of all-cause mortality between the IFNβ-1b 250 μg and placebo groups from the time of randomization through the entire 21-year follow-up interval (intention-to-treat, log-rank test for Kaplan-Meier survival curves). All other survival outcomes were secondary. Results: After a median of 21.1 years from RCT enrollment, 98.4%(366 of 372) of patients were identified, and, of these, 81 deaths were recorded (22.1% [81 of 366]). Patients originally randomly assigned to IFNβ-1b 250 μg showed a significant reduction in all-cause mortality over the 21-year period compared with placebo (p = 0.0173), with a hazard ratio of 0.532 (95% confidence interval 0.314–0.902). The hazard rate of death at long-term follow-up by Kaplan-Meier estimates was reduced by 46.8% among IFNβ-1b 250 μg–treated patients (46.0% among IFNβ-1b 50 μg–treated patients) compared with placebo. Baseline variables did not influence the observed treatment effect. Conclusions: There was a significant survival advantage in this cohort of patients receiving early IFNβ-1b treatment at either dose compared with placebo. Near-complete ascertainment, together with confirmatory findings from both active treatment groups, strengthens the evidence for an IFNβ-1b benefit on all-cause mortality. Classification of Evidence: This study provides Class III evidence that early treatment with IFNβ-1b is associated with prolonged survival in initially treatment-naive patients with relapsing-remitting multiple sclerosis. 16Y-LTF=16-Year Long-Term Follow-Up; 21Y-LTF=21-Year Long-Term Follow-Up; BOD=burden of disease; CI=confidence interval; DMT=disease-modifying therapy; EDSS=Expanded Disability Status Scale; HR=hazard ratio; IFNβ-1b=interferon β-1b; MS=multiple sclerosis; RCT=randomized clinical trial